Abstract

Substance identification N-Ethylnorpentylone (IUPAC name: 1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1-one) is a ring-substituted synthetic cathinone analog. It originally emerged in the 1960s during pharmaceutical drug development efforts. Another common name used widely is N- ethylpentylone. On the streets, N-ethylnorpentylone is most likely available as the racemic mixture and it might be obtained from Internet retailers. In the United States of America (USA), this substance was detected for the first time in 2014 but began to emerge more prominently in 2016 both in the USA and other UN Member States. Seizures indicate that N-ethylnorpentylone is available in powder, crystal, rock, capsule, and tablet forms. Examples exist where this drug has been surreptitiously sold as ‘ecstasy’/MDMA. WHO Review History N-Ethylnorpentylone has not been previously pre-reviewed or critically reviewed. Chemistry There is no specific information available about the routes of synthesis employed for the N- ethylnorpentylone products circulating on the drug market but straightforward methods for its preparation exist without requiring access to precursors that are controlled internationally. Ease of convertibility into controlled substances There is no specific information available but it appears unlikely that N-ethylnorpentylone is converted into a substance currently controlled under the UN conventions. Similarity to known substances / Effects on the central nervous system The information currently available suggests that N-ethylnorpentylone is a psychomotor stimulant and that its molecular mechanism of action is also shared by other ring-substituted synthetic cathinones of the pyrovalerone type, such as MDPV (1-(2H-1,3-benzodioxol-5-yl)-2-(pyrrolidin-1- yl)pentan-1-one) and α-PVP (1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one), which are both listed in Schedule II of the Convention on Psychotropic Substances of 1971. General pharmacology The number of systematic studies available at this time is limited but it seems clear that N- ethylnorpentylone is a psychomotor stimulant. In vitro, it has been demonstrated to block the reuptake of dopamine, norepinephrine and serotonin using rat brain synaptosomal preparations with preference for the dopamine system, thus, behaving cocaine- and MDPV-like rather than amphetamine-like. Animal studies confirmed that N-ethylnorpentylone increases locomotor activity and that it substituted for methamphetamine and cocaine in drug discrimination studies. Toxicology The LD50 value for N-ethylnorpentylone in the mouse (route of administration not reported) was determined at 240 mg/kg. Adverse reactions in humans The detection of N-ethylnorpentylone in biological fluids collected from cases involving adverse effects (including deaths) confirmed that this drug is circulating on the market and used recreationally. Not all of the reported adverse effects could be causally linked to N- ethylnorpentylone alone but there are indications that the observed effects are consistent with those seen with other psychomotor stimulants. The fact that N-ethylnorpentylone has been identified in products believed by users to represent ‘ecstasy’/MDMA means that users may be unaware of the additional risks of harm (e.g. potential exacerbation of a psychostimulant toxidrome) associated with the consumption of N-ethylnorpentylone either alone or in combination with other drugs. Dependence potential No studies carried out in humans or animals could be identified. Abuse potential In rodents, N-ethylnorpentylone fully substituted for methamphetamine and cocaine when using the drug discrimination paradigm. Mechanistically, results obtained from in vitro investigations confirmed that N-ethylnorpentylone inhibited the reuptake of the monoamines dopamine, norepinephrine and, to a lesser extent, serotonin, which is consistent with closely related pyrovalerone-type synthetic cathinones and cocaine with known abuse liability. The currently available data suggest that N-ethylnorpentylone might be liable to abuse. Therapeutic applications / usefulness N-Ethylnorpentylone is not known to have any therapeutic uses. Listing on WHO Model List of Essential Medicines N-Ethylnorpentylone is not listed. Marketing authorizations N-Ethylnorpentylone is not known to have any marketing authorizations. Industrial use N-Ethylnorpentylone is not known to have any agricultural, industrial or cosmetic uses even though it is available for purchase as a ‘research chemical’. Non-medical use The mode of use may involve the combinational use (intentionally or unintentionally) of other drugs and users may be unaware of the exact dose or compound being ingested (by whatever route). The information currently available suggests that N-ethylnorpentylone has been found in products sold as ‘ecstasy’/MDMA but there have been instances where other drugs have been detected in addition to N-ethylnorpentylone. N-Ethylnorpentylone may also be available in its own right and is advertised for sale by Internet retailers. Nature and magnitude of public health problems Use of N-ethylnorpentylone appears to be limited to recreational substance users rather than the general population. The mode of use may involve the combinational use (intentionally or unintentionally) of other drugs and users may be unaware of the exact dose or compound being ingested (by whatever route). The fact that N-ethylnorpentylone has been identified in products believed by users to represent ‘ecstasy’/MDMA means that users may be unaware of the additional risks of harm (e.g. potential exacerbation of central nervous system effects resulting in a psychostimulant toxidrome) associated with the consumption of N-ethylnorpentylone either alone or in combination with other drugs. Licit production, consumption, and international trade N-Ethylnorpentylone is not known to have any agricultural, industrial or cosmetic uses even though it is available for purchase as a ‘research chemical’. Illicit manufacture and traffic A dramatic increase in seizures and reports linked to the detection of N-ethylnorpentylone has been predominantly reported in the USA from 2016 onward. Purchase and importation of N- ethylnorpentylone is unproblematic in UN Member States that do not exercise legislative control measures. Increasing numbers of reports have appeared that document the detection of N- ethylnorpentylone on the drug market where it has been sold in the form of ‘ecstasy’/MDMA-like products. Current international controls and their impact N-Ethylnorpentylone is not controlled under the 1961, 1971 or 1988 United Nations Conventions. Current and past national controls N-Ethylnorpentylone is controlled in some UN Member States.